The available evidence indicates that sugammadex 16 mg kg−1
administered 3 or 5 min after an intubating dose of rocuronium produces a markedly faster recovery than placebo.10,11
In addition, one randomized trial indicates that recovery from rocuronium-induced block after administration of sugammadex 16 mg kg−1
is faster than spontaneous recovery from succinylcholine.12
On the basis of these trials, average recovery times appear to be fast enough to allow high-dose rocuronium to potentially replace succinylcholine in RSI as the block could be reversed rapidly with sugammadex if required. This could have important benefits in terms of reducing the morbidity and possibly mortality associated with the continuing use of succinylcholine. The rapid reversal of rocuronium-induced neuromuscular block by sugammadex 16 mg kg−1
could also be potentially life saving in a CICV situation during preparation for elective surgery. However, the evidence has important limitations as discussed below. The effectiveness of high-dose sugammadex in terms of facilitating the handling of emergencies and avoiding catastrophic events such as hypoxic brain damage is difficult to assess until the drug has been widely used in clinical practice.
The economic assessment was limited by a lack of suitable evidence and by uncertainty about where time savings associated with the use of sugammadex may be realized. As a result, we were not able to provide a definitive assessment of cost-effectiveness. Instead, a series of analyses was undertaken to explore the reduction in mortality required for sugammadex to appear cost-effective. Sugammadex appears more cost-effective for lower probabilities of a CICV event. This may seem counterintuitive but can be explained by the fact that the main economic benefit of sugammadex relates to the potential reductions in recovery time it can generate when surgery goes ahead. When a CICV event occurs, it is assumed that surgery is postponed and this benefit is not realized. Sugammadex also appears more cost-effective for younger patients and/or when the saved recovery time with sugammadex is achieved in the operating theatre rather than the recovery room. Except for those procedures where some saving in recovery time is achieved in the operating theatre, at least some reduction in mortality is required for sugammadex to appear cost-effective. This ranges from the prevention of one death in every 8790 uses of sugammadex (for 20-yr-old patients undertaking long procedures without the need for profound block, where there is no likelihood of a CICV event occurring and where the savings in recovery time are achieved in the recovery room) to the prevention of one death in every 1942 uses of sugammadex (for 60-yr-old patients undertaking very short procedures, where there is a 1% probability of a CICV event occurring). These results may be compared with the underlying risk of mortality with succinylcholine: where there is less than one mortality for every 8790 uses of succinylcholine, sugammadex does not appear cost-effective in any of these circumstances. However, where this underlying risk of mortality with succinylcholine is greater, sugammadex may appear cost-effective if the relative risk of mortality with sugammadex is sufficiently low. Unfortunately, there is little available evidence to inform either the underlying risk of mortality with succinylcholine or the relative risk of mortality with sugammadex compared with succinylcholine. It is not yet feasible to assess whether reductions in mortality risks necessary for sugammadex to be cost-effective (Table ) are realistic, as there have been too few administrations of the product for such estimates to be validated.
We used rigorous and systematic methods for searching for relevant studies, study selection, validity assessment, and data extraction. Study inclusion and exclusion criteria were specified in advance to reduce the risk of bias. Similarly, rigorous methods were used for the economic assessment. The limitations of both assessments reflect the limitations of the available evidence: more data were available to estimate costs than clinical events.
As a result of this lack of evidence, a decision about whether sugammadex is cost-effective requires an assessment of parameters whose value is unknown: for example, the underlying risk of mortality associated with the use of succinylcholine. We therefore attempted to establish the extent of the mortality reduction (relative to succinylcholine) required for sugammadex to be cost-effective. We modelled the probability of a CICV event across the range from 0 to 1%. It is recognized that, in practice, such events are very rare, particularly in specialist settings (e.g. a recent small UK study reported no failed intubations and only 23 difficult intubations in 3430 obstetric general anaesthetics).14
However, even with a very low risk, such events can be economically important and are therefore considered explicitly in the modelling.
As discussed elsewhere, there is also uncertainty about the extent to which time savings achieved by the use of sugammadex can be put to productive use.7
For example, there may be times when the patient is ready to be discharged from the operating theatre, but no bed is available in the recovery area. Therefore, to get the full economic benefit out of the potential reduction in recovery time associated with sugammadex, attention should be given to optimizing the flow of patients from the operating theatre to recovery.
The evaluation of sugammadex for immediate reversal after rapid induction of anaesthesia using rocuronium depends heavily on the single trial comparing rocuronium followed by sugammadex with succinylcholine followed by spontaneous recovery.12
Several uncertainties remain after publication of this trial. The primary outcome of the trial was time to recovery of T1/T0 to 0.1, but the clinical relevance of this endpoint is uncertain: although some signs of breathing may be present, T1/T0 of 0.1 does not represent a sufficient degree of recovery to allow safe extubation. However, the more clinically relevant endpoint of recovery of the TOF ratio to 0.9 was also measured in this study in the sugammadex group, giving a median of 1.7 min (range 0.48–14.3 min), similar to times reported in the placebo-controlled dose-finding studies. The wide range of times required to reach this endpoint could be of concern in clinical practice.
A potential issue with the use of sugammadex 16 mg kg−1 in an emergency is that the relevant clinical trials were only simulations of this situation and the appropriate dose of sugammadex was drawn up and ready for immediate administration. In routine practice, drawing up this dose in advance in anticipation of a very rare event would be wasteful and expensive. On the other hand, the time required to prepare the dose, including opening three ampoules and drawing the contents into a syringe, would increase the time the patient was exposed to hypoxia. The exact time this might take under the stress of an emergency situation is difficult to estimate.
Sugammadex 16 mg kg−1 can reverse the block induced with high-dose rocuronium shortly after it has been established. This cannot be achieved with any other reversal agent. Hence, sugammadex 16 mg kg−1 immediately after high-dose rocuronium could be considered a replacement for succinylcholine for RSI. This would avoid the morbidity associated with succinylcholine. The economic assessment suggests, however, that the cost-effectiveness of sugammadex will be highly sensitive to a given patient's underlying mortality risk during the procedure, so the drug may not be a cost-effective option in some patients at the current list prices for sugammadex. This option could be considered in the context of a clinical study at a limited number of centres.
Further research is needed to evaluate the effects of replacing succinylcholine by high-dose rocuronium and sugammadex on morbidity, mortality, patient-reported outcomes, and resource use. Further monitoring of adverse events associated with treatment with sugammadex is also needed, as the data available are limited for all doses but particularly for the 16 mg kg−1 dose. The range of recovery times recorded in the trials after administration of sugammadex 16 mg kg−1 suggests that an analysis of the proportion of patients who do not recover within, say, 5 min of administration of sugammadex, could be valuable.
The economic assessment of sugammadex for reversal after rapid induction of neuromuscular block was based on a series of analyses rather than a full cost-effectiveness model. Limited evidence was available to inform the modelling, and in particular, further research is required to define the baseline risk of mortality associated with succinylcholine in patients undergoing RSI and the relative risk of mortality with sugammadex. It should be emphasized that it is not yet feasible to assess whether reductions in mortality risks necessary for sugammadex to be cost-effective are realistic. This is because there have been too few administrations of the product for such estimates to be possible. A fuller economic assessment of sugammadex should be undertaken when more evidence is available, including evidence on resource use and the effects of sugammadex on health-related quality of life.